Combined gas chromatographic mass spectrometric methods previously developed for the assay of biogenic amines in various biological media have been employed to assess total body turnover of norepinephrine (sum NE) and dopamine (sum DA) in both human subjects and rats. We have also compared changes in sum NE and sum DA after a number of pharmacological manipulations in rats. The aim of these animal studies was to gain an insight into how these pharmacological treatments influence brain catecholamines in depression, schizophrenia and hyperactive children. (1) Consistent with our 1985 Annual Report, we have continued to gather additional supportive data that suggest a tendency for sum NE to be elevated in major depression. (2) Preliminary results sited in 1985 Annual Report on sum NE and sum DA in schizophrenia were substantiated. (3) Total body NE and DA turnover were assessed in both hyperactive children and adults after a number of pharmacological manipulations. The results indicated a correlation between therapeutic benefit and changes in both sum NE and DA irrespective of the direction of change. (4) The effects of four commonly used antidepressant treatments on rat peripheral and central catecholamines were evaluated. A good correlation between the effects of these drugs and sum NE and sum DA in humans and rats was observed. It is suggested that because of this correlation, changes in the rat brain amines observed probably resemble the changes these treatments induce in the human brain. The four treatments employed were chronic zimelidine, desipramine, electroconvulsion and lithium.